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Summary Background The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults. Methods In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18–50 years with a body-mass index of 18·0–35·0 kg/m2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1–4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538. Findings Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3–735·1) for cohort 1, 466·3 h (382·8–522·3) for cohort 2, 397·0 h (333·9–491·8) for cohort 3, and 466·7 h (351·0–889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6–592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study. Interpretation Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections. Funding Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program.

Although there is a substantial research literature on the effects of random responding on the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen,Kaemmer, 1989), there are very few studies available on this topic with the MMPI-A (Butcher et al., 1992). Archer and Elkins (1999) found that MMPI-A validity scales F and VRIN were particularly useful in detecting entirely random profiles from those derived standardly in clinical settings but noted that "all random" protocols could not be used to evaluate the usefulness of the T-score difference between the first half (F1) and the second half (F2) of the MMPI-A test booklet. Following up on this issue, this study extended the methodology of previous research by examining the hit rate, positive predictive power, negative predictive power, sensitivity, and specificity of VRIN, F, F1, F2 and the absolute value of the T-score difference between F1 and F2 (denoted as IF1-F21) in 5 samples varying in the degree of protocol randomness. One of the samples consisted of 100 adolescent inpatients administered the MMPI-A under standard instructions, and another sample consisted of 100 protocols randomly generated by computer. The additional 3 samples of 100 protocols each contained varying degrees of computer-generated randomness introduced in the latter half of the MMPI-A item pool. Over- all, the results generally indicate that several MMPI-A validity scales are useful in detecting protocols that are largely random, but all of these validity scales are more limited in detecting partially random responding that involves less than half the total item pool located in the second half of the test booklet. Clinicians should be particularly cautious concerning validity inferences based on the observed T-score difference that occurs for the F1 and F2 subscales and current findings do not support the clinical usefulness of this index.

The Minnesota Multiphasic Personality Inventory-Adolescent (MMPI-A; Butcher et al., 1992) was released in 1992 and has rapidly become the most widely used objective personality assessment instrument with adolescents. Although the MMPI-A reduced or eliminated several problems associated with the use of the original MMPI (Hathaway & McKinley, 1943) with adolescents, the MMPI-A does produce a high frequency of within normal limits basic scale profiles for individuals with substantial psychopathology including adolescents in inpatient psychiatric settings. To better understand the reasons for this phenomenon, we compared the item endorsement frequencies for the MMPI-A normative sample with results from two adolescent clinical samples, and these results were contrasted to the item endorsement frequencies for the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) normative sample and a clinical sample of adult psychiatric inpatients. Results showed that the MMPI-A contains a substantial number of items that do not show a significant difference in item endorsement frequency between normative and clinical samples. Furthermore, MMPI-A basic and content scales generally show a much lower percentage of effective items than do the corresponding scales for the MMPI-2. We discuss the findings in relation to the frequent occurrence of low range MMPI-A profiles in clinical samples and the potential usefulness of these results in future efforts to develop viable short forms for the MMPI-A.